Contribution of large animal models to the development of clinical intestinal transplantation

The intestine has long been seen as a "forbiddeif' organ to transplant and even nowadays it remains the most challenging abdominal organ to transplant. Large animal experiments have been pivotal, first in developing reproducible and clinically applicable surgical techniques for transplanting the intestine and second, in revealing the unique physiological, immunological, and microbiological challenge that intestinal transplantation (lTx) represents. More recently, large animal models have been used to test new immunosuppressive drugs (FK 506) that have been then successfully used clinically. lTx is no more an experimental endeavor and survival figures of about 70 % can be reached at one year, justifying routine application of lTx to patients who do not tolerate total parenteral nutrition. However lTx remains in 1999 an "unfinished producf' and further rssearch will need to be done to allow wider application of lTx to patients without total parenteral nutrition (TPN) related complications. Further research will focus on the following aspects : (1) refined understanding of the factors accounting for the high immunoge@city of the intestine; (2) development of immunomodulatory strategies to reduce graft immunogenicity and to induce specific hyporesponsiveness; (3) development of new immtmosuppressants, and their usage in combination, to act more specifically on the immune response, and at the price of less toxicity ; (4) development of surgical alternatives to alleviate the organ shortage : graft size reduction, live related lTx. Importantly these questions will need to be addressed in clinically relevant animal models before they are applied to man.